The publications and other materials used herein to illuminate the background of the invention, and in particular, the cases to provide additional details respecting the practice, are incorporated by reference. Especially the patents U.S. Pat. No. 6,056,976 and U.S. Pat. No. 6,299,894 as well as the pending applications, U.S. Ser. No. 09/701,547, filed Nov. 30, 2000 (equivalent: WO 00/00550) and WO03/017971 are incorporated by reference.
The concept of treating sudden deafness, Meniere's disease and tinnitus, which are considered to have the same etiology, with corticosteroids applied in the middle ear for perfusion through the round window membrane, has been presented as the future treatment. Sudden deafness has an annual incidence of 2:10 000 and Meniere's disease has an estimated annual incidence of 1:5 000, but because of the chronic nature of this condition, the prevalence figures are much higher. In Germany, about 20 000 patients (on 80 million inhabitants) seek treatment for tinnitus every year, these figures including the severe cases only.
Several publications disclose different devices to be placed in the ear of patients suffering from sudden deafness, Meniere's disease, tinnitus or other ear disorders (such as endolymphatic hydrops, endolymphatic hypertension, perilymphatic hypertension, perilymphatic hydrops, perilymphatic fistula, intracochlear fistula, vertigo, hearing loss related to hair cell or ganglion cell damage or malfunction). Such devices allow the delivery of therapeutic agents to various ear tissues in a controlled manner. For example, a variety of structures have been developed which are capable of delivering therapeutic agents into the external auditory canal of the outer ear or to tissue structures of the inner ear. The same situation exists with tissue materials that lead into the inner ear (e. g. the round window membrane).
Inner ear tissue structures suitable for this kind of treatment comprise the cochlea, the endolymphatic sac/duct and the vestibular labyrinth. Access to these and other inner ear tissue regions is typically achieved through a variety of structures, including but not limited to the round window membrane, the oval window/stapes footplate, the annular ligament, and the otic capsule/temporal bone. Furthermore, the middle ear that is here defined as the physiological air-containing tissue zone behind the tympanic membrane and ahead of the inner ear, may also be used for the delivery of therapeutic agents. One particularity of the ear and the nose, when compared to subcutaneous positioning of delivery devices, is that there are no body fluids that induce and help the release of the active agent and convey it to the target organ.
Corticosteroids are commonly used to treat these diseases. Said devices can be placed in the round window niche or other internal ear cavity.
The U.S. Pat. No. 6,120,484 discloses an otological implant for delivery of a medicament comprising a wick inserted through an aperture in a membrane. One end (distal end) of the wick is in contact with the treatment site and the other end (proximal end) is accessible for contacting with a medicament source. The wick conveys the medicament from the proximal end to the distal end by capillary action. The wick is made for example of polyvinyl acetate, a material that is capable of conveying the medicament by capillary action. The implant may further include a tube member for supporting the wick, said tube being made of silicone, for example. The document does not mention how to regulate the release rate of the medicament.
On the other hand, the patent application WO 00/33775 presents a device for controlled delivery of a therapeutic agent to an internal cavity of the ear. The device is placed so that at least a portion thereof is in the round window niche. The released therapeutic agents come in contact with the round window niche and pass therethrough into the inner ear. The device consists essentially of a carrier media that is combined with said agent. The carrier media may comprise biodegradable material and at least one material of synthetic origin. Said materials may be polymeric materials that are cross-linked and that swell when in contact with water in the body temperature. The application discloses different methods for the release of the agent, such as diffusion, solvent drag, electrodiffusion, osmosis, active/passive transport or a combination thereof. This document discloses that the agent that is positioned deepest in the device, release the slowest. The release rate of the agent thus relates to its relative position within the device, i.e. it relates to the distance to the outer surface of the device.
It is also known from the literature that implants may be used in the nose for controlled delivery of pharmaceutical drugs. An example of such implants is given in the U.S. Pat. No. RE35,408 which presents a metallic nasal drug delivery device comprising end portions in the form of relatively thin tabs. A preferred material for the end portions is silicone rubber (Silastic®). The pharmaceutical drug is contained in surface cavities or pockets or in the coating of the surface.